反应详情

温度

-10 °C

To a stirred solution of (R)-2-[4-({[2-(benzo[1,3]dioxol-5-yloxy)-pyridine-3-carbonyl]-amino}-methyl)-3-fluoro-phenoxy]-propionic acid (0.25 g, 0.55 mmol) in ethylene glycol dimethyl ether (20 mL) at −10° C. was added N-methyl morpholine (0.06 mL, 0.55 mmol) followed by dropwise addition of isobutyl chloroformate (0.071 mL, 0.55 mmol). The turbid solution was stirred at −10° C. 10 min. Ammonia gas was bubbled through the reaction mixture 10 min, which was then warmed to room temperature and stirred a further 15 min. The reaction mixture was partitioned between chloroform and water. The organic layer was dried over sodium sulfate and concentrated in vacuo to afford a white solid. Flash column chromatography (1% methanol/dichloromethane) yielded 0.15 g of a white solid (60% yield).

1. custom10 min
2. customAmmonia gas was bubbled through the reaction mixture 10 min, which
3. temperaturewas then warmed to room temperature
4. stirringstirred a further 15 min
5. customThe reaction mixture was partitioned between chloroform and water
6. dry with materialThe organic layer was dried over sodium sulfate
7. concentrationconcentrated in vacuo
8. customto afford a white solid